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Potential Immunotherapy for Prostate Cancer: Recombinant Bacille Calmette-Guerin Expressing Prostate Specific Molecules

Christina Zeoli-Costa, Henry P. Godfrey, Michael Iatropoulos, Polly Gregor, Abraham Mittelman, Jan Geliebter

Abstract


Purpose: The emergence of prostate cancer as a major health issue and the absence of curative treatment for metastatic disease requires the development of new treatment modalities. Prostate specific antigen (PSA) and prostate-specific membrane antigen (PSMA) are possible targets for prostate cancer immunotherapy. We have previously shown that PSA and PSMA can be expressed in recombinant bacille Calmette-Guérin (BCG) strains.

Methods: The in vivo immunogenicity of the prostate-specific proteins produced by this recombinant BCG strain were examined by detection of specific antibody responses and delayed-type hypersensitivity (DTH) responses in mice vaccinated with these strains. These immune responses were compared with those of control mice vaccinated with phosphate buffered saline diluent or soluble PSA or PSMA.

Results: Mice vaccinated with rBCG-PSA developed low levels of anti-PSA antibodies and strong DTH to PSA.  Mice vaccinated with rBCG-PSMA developed strong DTH to PSMA and no anti-PSMA antibodies. 

Conclusions: We conclude that recombinant BCG expressing PSA or PSMA induce strong cellular immune responses to these antigens. We propose that the innate adjuvant capacity of BCG could help stimulate a specific immune response against prostate-specific proteins produced by the bacteria, which in turn, could lead to the eradication of undetected metastatic prostate cancer cells in post-surgical patients.


Keywords


prostate cancer; BCG; bacille Calmette-Guerin; PSA; prostate specific antigen; PSMA; prostate-specific membrane antigen; immunotherapy

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